Chemo After Breast Cancer Surgery - The State of the Art

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Right after the 2006 San Antonio Breast Cancer Symposium, HealthTalk spoke with leading breast cancer specialist Dr. Joyce O'Shaugnessy about what's new in adjuvant therapy, which is chemotherapy given after surgery for breast cancer. Find out what’s new. What could recent treatment news mean for you?

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This transcript was edited from the original audio for clarity and readability and may not exactly match the audio version of the show.

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Rick Turner:
Hello, and welcome. Just last week [December 14-17, 2006], cancer specialists gathered at the San Antonio Breast Cancer Symposium to discuss the ever-changing treatment and research landscape. Joining us today to help explain adjuvant therapy developments that came out of this year’s symposium is Dr. Joyce O’Shaughnessy, a medical oncologist specializing in breast cancer with Texas Oncology, US Oncology and the Baylor-Sammons Cancer Center in Dallas. She is co-chair of breast cancer research for the US Oncology Clinical Trials Network, which enrolls more than 1,400 patients annually in breast cancer treatment and risk reduction trials. She is also director of Cancer Prevention Research at Baylor-Sammons Cancer Center. Dr. O’Shaughnessy, welcome to the program.

Dr. Joyce O’Shaughnessy: Thank you very much. Glad to be here.

Rick:
I’m glad to have you with us. Today, we’re discussing advances in adjuvant therapy, which is additional medical treatment that is typically given following surgery, is that correct?

Dr. O’Shaughnessy:That’s correct.

Rick:
So let’s jump right into the news of this year. Now, Dr. O’Shaughnessy, you attended the symposium in San Antonio. Can you please summarize for us the top adjuvant therapy headlines, including adjuvant therapy for the HER-2-positive patient?

Dr. O’Shaughnessy:
The biggest news from San Antonio this year was a study called the BCIRG 006 trial. People who are interested in seeing that information first-hand can do a Google search on BCIRG (bcirg.org), which stands for the Breast Cancer International Research Group, and you can see the slides for themselves.

This was a very important trial that was done in the 20 percent of breast cancers that are actually driven by a gene called the HER-2. This is not one of those genes that’s inherited from in the family. It’s a gene that happens to occur in 20 percent of breast cancers. We actually don’t know why these breast cancers develop because of this gene. [Medical editor’s note: The HER-2 gene causes the production of a protein receptor that sits on the outer membrane of the cancer cells. HER-2 receptors are present on some normal cells, and they respond to signals that tell the cell to divide and multiply. HER-2-positive cancer cells have an extremely increased number of HER-2 receptors, which are constantly signaling the tumor cells to grow.]

There is a very important antibody treatment called Herceptin (trastuzumab) that binds to the HER-2 protein receptor, which basically inactivates that receptor, so it cannot respond to the signals telling the cell to divide. This inhibits the cancer growth.

When you put the Herceptin together with chemotherapy in the treatment of early breast cancer that’s HER-2-positive, you get a much better outcome than just treating them with chemotherapy alone. The addition of Herceptin to chemotherapy for early breast cancer has been a huge advance and has really improved the outcome dramatically in HER-2-positive patients.

At San Antonio this year, the BCIRG 006 trial was updated. This was interesting because of the big toxicity that we worry about when Herceptin is combined with one of the chemotherapy drugs called taxanes, Taxotere (docetaxel) or Taxol (paclitaxel). The toxicity can occur if this combination is given to a patient after they have received two very commonly used chemotherapy agents have been used, Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), which is a combination known as AC. When you give the Herceptin combination after AC, about 3 to 4 percent of women will develop congestive heart failure. This is a very serious toxicity. And as women get older, the risk goes up. If they’re younger, it goes down. Most of the patients seem to recover the normal function of their heart with treatment by a cardiologist. But some women still require cardiac medications after they are treated for this congestive heart failure. It’s very rarely fatal, but it still is very important because it means stopping the Herceptin and the chemotherapy and getting on cardiac medications.

The BCIRG study compared a standard chemotherapy regimen, four cycles of AC, followed by four cycles of taxotere. That’s been a very standard regimen for quite a while. Then, they compared that to AC for four cycles, followed by the taxotere with the Herceptin. That was pretty standard, and we know that adding Herceptin to the taxotere makes a very large difference in terms of improving women’s outcomes. But you still run that risk of congestive heart failure.

Then, there was a third option in that trial that women were randomized to. This third option was taxotere, carboplatin (Paraplatin) and Herceptin. Essentially, you get rid of the Adriamycin. As a result, there was much less congestive heart failure. It was extremely rare, in fact, to have any cardiac problems with the so-called TCH - taxotere, carboplatin and Herceptin - combination. Everybody was hoping that the TCH treatment would be as good as the AC followed by the Taxotere/Herceptin because you’d love to have treatment that was equally as good, but not causing problems for the heart. That actually was what was seen at the presentation. This was with the average woman being followed up three years after her diagnosis of breast cancer. So it is still pretty early. What was seen was that the two Herceptin options - the TCH and the AC followed by the taxotere/Herceptin - were equally efficacious, which was great news. But the TCH was a lot less toxic on the heart, which was expected and really great to see.

In the research setting, they were looking at another gene, a gene that is different than the HER-2, called TOPO2. TOPO2 is the actual protein that Adriamycin attacks when trying to kill off the cancer. So the question was this: In the breast cancers that were HER-2-positive that also had an excess amount of TOPO2, maybe they would really need that Adriamycin because Adriamycin - that’s the protein that the Adriamycin attacks. Well, the BCIRG looked at that in all the arms of the trial and, in fact, even in the patients who had an excess amount of TOPO2. [Medical editor’s note: Roughly 35 percent of the HER-2-positive patients had excess TOPO2]. They did equally well with the TCH without the Adriamycin. So that was quite gratifying because it shows that not attacking the TOPO2 with Adriamycin was not a problem.

What this does is that it gives us an opportunity now to utilize the TCH regimen without the Adriamycin for our patients with HER-2-positive breast cancer. We are giving very serious consideration in our research network of using TCH exclusively in our clinical trials in the HER-2-positive patients. For the patient with node-negative breast cancer or patients with lower risk node-positive breast cancer, personally I think the TCH regimen is really a very viable option. I think that’s going to be practice-changing. I think we’re going to see much more use of the TCH regimen because the physicians are really keen to give women the best outcomes without causing problems with their hearts.

That was the most important bit of information coming out of the San Antonio meetings, Rick.

Rick:
Dr. O’Shaughnessy, was there any other significant news that you heard with regard to adjuvant therapy specifically?

Dr. O’Shaughnessy: The next biggest piece of news was an update of the WINS trial, the Women’s Interventional Nutrition Study. This was a study presented by Dr. Rowan Chlebowski from UCLA. The women in the WINS study were breast cancer survivors who had finished up their treatment with chemotherapy and were on anti-estrogen (hormonal) therapy if they were hormone receptor-positive. If they were hormone receptor-negative, they were not getting anti-estrogen therapy, or they weren’t required to have had adjuvant chemotherapy.

The women who were survivors, who showed no evidence of any disease, were randomly given either basic information about a good nutritional diet, or they were randomized to an intensive intervention and contact with the dietician to help them eat a low-fat diet of only 35 fat grams a day. Most of us eat 55 to 60 fat grams a day, so this was a low-fat diet. This group of patients required meeting with the dietician every two weeks for four times, and then I think it’s monthly calls from the dietician thereafter for the five years of the study to really make sure that the women were adhering to the low-fat diet. In fact, the women were largely able to adhere to that low-fat diet. In the overall study, there was a significant benefit in terms of the reduction in the risk of recurrence. Eating a low-fat diet significantly reduced the risk of the cancer recurring.

What was particularly interesting is in the women with estrogen receptor-negative breast cancer there was a very large reduction in the risk of recurrence or death. There was a 50 percent reduction in the risk of relapse or death. Additionally, there was an 11percent absolute decline in the risk of death. This is really big news because a low-fat diet is certainly something that a woman could do for herself. Generally speaking, we think it is important to have some dietary consultation at your hospital. Your oncologist could make a referral to a local dietician for help with that low-fat diet. This is a very major step forward, particularly for the ER-negative patients. The ER-positive patients are treated with hormonal therapy, either tamoxifen (Nolvadex) or one of the aromatase inhibitors (AIs), and the ER-negative patients oftentimes are treated with chemotherapy. But when they finish the chemotherapy, we don’t have any additional treatment for them. So this low-fat is very compelling. These are very exciting results.

We’re not sure why eating a low-fat diet makes a difference. The best hypothesis that we have is that a low-fat diet lowers the insulin levels in our bodies. We do know that insulin is a growth factor for breast cancers - both ER-positive and ER-negative breast cancers. So that’s our best hypothesis, but that’s not really proven yet. But other things like exercise - walking three hours a week at a moderate pace - we also believe can reduce the death rate from breast cancer. We think that walking reduces insulin levels. There definitely are things that women can do to improve their chances of long-term disease-free survival from breast cancer. That was also very exciting information.

Rick:
Those are promising results. Do you think, Dr. O’Shaughnessy, that these advances in treatments and approaches are going to impact how people are treated today?

Dr. O’Shaughnessy:
Yes, I definitely do. We got the good results from the WINS trial about a year ago. And since that time, I’ve talked to all of my patients about a low-fat diet and about walking three hours a week. I intend now to print out from the San Antonio Web site this information on the WINS trial and give it to all my women while emphasizing that this is remarkable. This is truly remarkable information. It’s really important that we not only just try to kill off the cancer cells, we have to take care of the woman.

With regard to the BCIRG study, I do think that the TCH regimen - taxotere (docetaxel), carboplatin (Paraplatin) and Herceptin (trastuzumab) - will be utilized more. It’s very exciting to see how well the women did with the TCH. It really suggests the role of Adriamycin (doxorubicin) going forward, and I think that that’s a very important question. Again, we only have three years of follow-up on this trial, and I think that it would be certainly reasonable for physicians to continue to use the AC followed by either taxotere or Taxol (paclitaxel) with Herceptin. But I think it’s equally reasonable now to use the TCH for lower risk women. In women who have a risk for cardiac problems or lower risk women, I think the TCH regimen really is an important advance.

Rick:
As people in our audience hear this news about promising results from clinical trials, what does that mean in terms of when this therapy might be available to them? Does it mean now or soon? What should they think?

Dr. O’Shaughnessy:
Oh, it’s available now. In fact, all women who are diagnosed today with HER-2-positive breast cancer, which is about 20 percent of the breast cancers, can receive this excellent treatment right away. The treatment I was speaking about - the TCH regimen - is available to all of us, as is the AC followed by the taxotere or Taxol with Herceptin regimen.

With regard to the low-fat diet, women can pick up a fat-gram counter from their local bookstore so that they can familiarize themselves with the fat-gram content of foods. I do think it is important to get a referral from your oncologist or primary care physician for dietary consultation, so you can really get an understanding of how to eat a low-fat diet that provides only 35 fat grams a day.

Rick:
For people living with breast cancer, what do these results mean bottom line? Can they look forward to a better survival rate and improved quality of life?

Dr. O’Shaughnessy:
Yes, I definitely think so. Both of these trials that I’ve discussed talk about major improvements in survival for breast cancer. There are a number of other agents that are in clinical trials now that we’re very optimistic will lead to further improvements in survival, not only for the HER-2-positive population, but women with ER-positive (estrogen-receptor positive) breast cancer who already have an excellent outcome from their breast cancer because of the very good anti-estrogen therapies that we have now.

There was other very good news at the San Antonio meeting. Since 2003, every single year the death rate from breast cancer has been falling. The death rate started falling in the late ‘90s. But just since 2003, the number of women who develop breast cancer in the United States has been actually significantly declining. We’re down to 7 percent less breast cancer since 2003. This is hypothesized to be mainly due to the fact that the use of hormone replacement therapy after menopause, particularly combined estrogen and progesterone, has dramatically declined since the Women’s Health Initiative data in 2002 were released. That data showed an increased risk of breast cancer with the combined estrogen and progesterone after menopause. Interestingly, that was not seen with estrogen alone. So many millions of women stopped taking hormone replacement therapy after menopause in 2002. This was reflected as early as 2003, with a very nice reduction in breast cancer incidence that is continuing to decline.

Rick:
Dr. O’Shaughnessy, given the latest news in San Antonio at the symposium, are you optimistic about the future of breast cancer treatment?

Dr. O’Shaughnessy:I really am. I think the thing that I’m most optimistic about is what I was talking about with the HER-2-positive breast cancer. The reason we’ve been able to make such great progress against that particular subset of breast cancers is because we’ve been able to identify the HER-2 as the key molecule that leads to the survival and the growth of those breast cancers. So the reason I’m optimistic is that our ability to do more discerning diagnosis, about the kind of breast cancer that a woman has, and the genes and proteins driving that breast cancer is advancing. It is not here now for all women. But the molecular tools are in place, and a huge amount of research is going on. Most importantly, as we identify the key molecules that are driving these breast cancers, we already have inhibitors of these molecules in clinical trials. So it’s really just a question of connecting the dots at this time.

Rick: The more discerning you can be in your analysis of these various cancers should translate to therapy that is less toxic and more targeted, correct?

Dr. O’Shaughnessy: Exactly, that is correct.

Rick:
Thanks so much for the update, Dr. O’Shaughnessy. Our guest has been Dr. Joyce O’Shaughnessy, a medical oncologist specializing in breast cancer with Texas Oncology and US Oncology at the Baylor-Sammons Cancer Center in Dallas. From all of us at HealthTalk, thank you for joining us. We wish you and your family the best of health.

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